Dietary fat and cholesterol effects on cholesterol metabolism in CBA/J and C57BR/cdJ mice

The aim of this study was to determine how small differences in dietary fats affect cholesterol metabolism in mice hypo- (CBA/J) and hyperresponsive (C57BR/cdJ) to diet-induced hypercholesterolemia. Six-wk-old male mice were fed either a diet corresponding to the U.S. average gross composition (US74, 40% of total energy as fat, 347 mg cholesterol/1000 Kcal, P/S = 0.24) or a modified-fat diet (30% of total energy as fat, 46 mg cholesterol/1000 Kcal, P/S = 0.91). After 8 wk of feeding, neither strain had developed hypercholesterolemia. CBA/J mice had higher concentrations of serum total and high-density lipoprotein (HDL) cholesterol and a higher esterified-to-free cholesterol ratio than did C57BR/cdJ mice. CBA/J mice maintained a constant serum cholesterol concentration mainly by adjusting the hepatic hydroxymethylglutaryl coenzyme A reductase (HMGR) activity, whereas C57BR/cdJ mice did so by changing the fecal excretion of cholesterol. Compared to the modified-fat diet, the US74 diet caused an increase in the ratio of total to HDL serum cholesterol, liver microsomal free cholesterol, fecal cholesterol and hepatic microsomal cholesterol 7 alpha-hydroxylase activity and a decrease in hepatic microsomal HMGR activity. We conclude that the metabolic responses to small differences in dietary fat are different in CBA/J and C57BR/cdJ mice.